RNA viral diseases are responsible for the vast majority of viral morbidity and mortality of viral diseases of mankind, including AIDS, hepatitis, rhinovirus infections of the respiratory tract, flu, measles, polio and others. There are a number of other chronic persistent diseases caused by RNA or DNA viruses that replicate through an RNA intermediate which are difficult to treat, such as hepatitis B and C, and T-cell human leukemia. A number of common human diseases are caused by RNA viruses that are replicated by a viral encoded RNA replicase. Included in this group are influenza (Zurcher, et al., J. Gen. Virol. 77:1745 (1996), dengue fever (Becker, Virus-Genes 9:33 (1994), and rhinovirus infections (Horsnell, et al., J. Gen. Virol., 76:2549 (1995). Important RNA viral diseases of animals include feline leukemia and immunodeficiency, Visna maedi of sheep, bovine viral diarrhea, bovine mucosal disease, and bovine leukemia. Although some vaccines are available for DNA viruses, diseases such as hepatitis B are still prevalent. Hepatitis B is caused by a DNA virus that replicates its genome through an RNA intermediate (Summers and Mason, Cell 29:4003 (1982). While an effective vaccine exists as a preventive, there is no efficacious treatment for chronic persistent HBV infection.
Currently there is no effective therapy for many viral diseases. While vaccination against influenza can be effective, a new vaccine must be generated each year, depending on the mutations that were fixed in the circulating strain in the previous year, a consequence of the rapid evolution of the viral genome. Current treatment of hepatitis C employs interferon, but it is seldom curative for the disease.
Thus, there exists a need for an effective prevention or amelioration of RNA and DNA virus mediated diseases. The present invention satisfies this need and provides related advantages as well.